Within the Center for Biomedical Mass Spectrometry, the BUSM Mass Spectrometry Shared Instrumentation Laboratory operates three mass spectrometers (a Thermo-Fisher LTQ-Orbitrap, a Bruker Daltonics Reflex IV MALDI-TOF MS and a Bruker SolariX 12-T UPLC-FTMS), that are dedicated to meeting the increasing and complex needs of NIH-funded investigators. We propose to replace and upgrade the 11-year-old Reflex IV by purchasing and installing a Bruker Daltonics ultrafleXtreme MALDI-TOF/TOF Mass Spectrometer system to provide reliability and access to support services that are no longer available for the Reflex IV and to give improved sensitivity and the additional capabilities for obtaining high resolution mass spectra, tandem mass spectra and two-dimensional imaging. This system will offer high throughput, will facilitate the identification of peaks observed in MALDI-TOF mass spectra to assist in the structural determinations of post-translationally modified proteins and structure elucidation of carbohydrates and glycolipids, and will enable imaging of 2-D samples, to support the human health-related projects described in this proposal. The system will furnish MS and MS/MS spectra and surveys of 2-D targets such as protein arrays, thin layer chromatographic plates and tissue samples. The requested system will improve the efficiency of the Mass Spectrometry Shared Instrumentation Laboratory because unknown peaks will be able to be identified directly from MALDI MS data, thus shortening analysis time, diminishing the need for subsequent LC/MS/MS analyses and increasing the information that can be obtained for samples that are not appropriate for electrospray ionization. The research topics include Cardiovascular Disease, Alzheimer Disease, familial and sporadic systemic amyloid diseases, prion diseases, Cancer, Huntington Disease, Lyme and Rheumatoid Arthritis, Sickle Cell Disease, Traumatic Brain Injury, infectious diseases and characterization of protective components in human milk. Ten Major and six Minor research projects are proposed. All investigators are currently involved in research projects that rely upon the Reflex IV MALDI-TOF MS system that will be retired. Most of the investigators are located on the BUSM campus; the projects the four outside investigators, who are located at the Boston University Charles River Campus, Boston College and Harvard Medical School, have joint funding with CBMS investigators. PUBLIC HEALTH RELEVANCE: The clinical and basic research of the Major Users includes cardiovascular disease (Cohen), (Cohen), cancer (Goldberg) Alzheimer Disease and Traumatic Brain Injury (Goldstein), protein misfolding in prion and systemic amyloid diseases (Harris, Seldin) protective components in human milk (Newburg), Lyme disease and rheumatoid arthritis (Steere), other infectious organisms (Samuelson and Robbins), and wound healing in the eye (Trinkaus-Randall). Projects of the Minor Users address leukemia and breast cancer (Denis, Lerner), sexually transmitted disease (Fichorova), tumor growth (Rahimi), sickle cell disease (Steinberg), and Huntington Disease (Sherman). The proposed instrument system will accelerate progress towards diagnosis and treatment based on understanding the mechanisms of these diseases and conditions and will thus contribute directly toward improving human health.